A recent report written by John Sweetenham, MD, in HemOnc Today, revealed that progress is being made concerning the endpoints of clinical priority studies of follicular lymphoma (FL), which has improved overall survival rate of patients suffering from FL.
Lymphoma is considered the most common blood cancer, with follicular lymphoma accounting as a prevalent form of indolent non-Hodgkin’s lymphoma. Usually lymphoma develops when white blood cells (lymphocytes) of the immune system multiply uncontrollably and travel to reach multiple parts of the body like lymph nodes, spleen, bone marrow, blood, or other organs to form a tumor mass. Patients with FL suffer from enlargement of lymph nodes in the neck, underarm, stomach, or groin. The latter may yield symptoms of fatigue, shortness of breath, weight loss, and night sweats. From the therapeutic view point, several treatments for FL are available depending on severity of the cancer growth and the induced symptoms. If patients experience no symptoms, physicians may decide not to treat the disease, since studies have showed no differences in outcomes for patients with or without treatment at these early stages. However, if symptoms emerge, radiation can cure patients with limited disease progression and at advanced stages one or more chemotherapy drugs like R-CHOP or monoclonal antibody rituximab (Rituxan) could be administrated.
Statistics suggest that median survival for patients with FL is around 10 years, but this ranges from less than one year to more than 20 years. However, when compared to past decades, recent studies reveal that survival rate of patients with FL has increased. The primary reasons behind this improvement lie in the introduction of monoclonal antibodies as well as progress in therapy development.
The number of clinical trials for FL has dramatically increased in recent years and the measure of treatment efficiency on a disease, the so called PFS (progress free survival), is a widely acceptable endpoint for most of these studies. For example, R-CHOP drugs utilized in chemotherapy often yield median PFS rates of 5 to 8 years, which is considered a long waiting time to observe an effect for an early intervention. This induces frustration in patients expecting novel treatments with quick clinical outcomes. Hence, the search for surrogate endpoints with early readouts from trials in FL has been the subject of intense investigation, with data from some recent reports showing signs of progress.
For example, a recent presentation given during ASCO’s Annual Meeting highlighted the potential utility of complete remission of trial data after only 30 months (CR30) from the beginning of therapy as surrogate for long term PFS. Other data published in the Journal of Clinical Oncology reported that disease progression within 2 years of diagnosis served as a primary endpoint. Unfortunately, these studies lack data from imaging. Additional reports have demonstrated that post-treatment using positron emission tomography (PET) scanning in patients with high tumor load should be considered as another potential early surrogate for PFS in FL. Finally, encouraging data have also been published with concerning the use of minimal residual disease measurement by polymerase chain reaction as a predictor of PFS as well as a possible measurement of circulating tumor DNA in B cell lymphoma.
Altogether these data suggest that CR30 could be a highly compelling surrogate for PFS with the potential to become a widely accepted primary endpoint in clinical studies. If confirmed, it would fulfill the need for an earlier readout. On the other hand, functional imaging or molecular based methods have to provide reliable primary endpoints in FL before being further considered.